Evaluation of Automated Delivery of Propofol Using Closed-Loop Anaesthesia Delivery System in Patients Undergoing Thoracic Surgery: A Randomised Controlled Study

Evaluation of Automated Propofol Delivery in Patients Undergoing Thoracic Surgery



Sponsors

Lead Sponsor



Source

Sir Ganga Ram Hospital

Oversight Info

Has Dmc

Yes

Is Fda Regulated Drug

No

Is Fda Regulated Device

No

Is Us Export

No


Brief Summary

Automated delivery of propofol using computer-controlled closed loop anaesthesia device
delivers propofol based on patient's frontal cortex electrical activity as determined by
bi-spectral index (BIS). Evaluation of anaesthesia delivery by these systems has shown that
they deliver propofol and maintain depth of anaesthesia with far more precision as compared
to manual administration.

By automatically controlling anaesthesia depth consistency they provide time to the
anaesthesiologist to focus on other aspects of patient care such as managing intra-operative
hemodynamics and ventilation perturbations during major surgeries.

Closed loop anaesthesia delivery system (CLADS) is an indigenously developed continuous
automated intravenous infusion system which delivers propofol based on patients EEG profile
(BIS) feedback. Although a few studies have already evaluated these automated systems in
patients undergoing thoracic surgery, but suffered from significant limitations (small number
of patients, not dedicated to thoracic surgery cohort). Currently, there is no data available
regarding CLADS performance vis a vis adequacy of GA and haemodynamic profile in patients
undergoing thoracic surgery.

We contend that propofol as delivered by CLADS will proffer greater consistency to
anaesthesia depth, intra-operative hemodynamic stability, and rapid recovery upon anaesthesia
discontinuation than manual means of delivering propofol TIVA. This randomised controlled
study aims to compare the efficiency of CLADS-driven propofol TIVA versus manually controlled
propofol TIVA in patients undergoing thoracic surgery.

Detailed Description

After Ethics Committee approval and written informed consent, thirty-participants (30 per
group) aged 18-65 years, ASA physical status I-III, of either sex, and undergoing unilateral
open thoracic surgery or unilateral video-assisted thoracic surgery (VATS) will be included
in this single centre (Sir Ganga Ram Hospital, New Delhi-110060, India) prospective,
single-blinded, two-arm, randomised controlled study.

The patients who qualify inclusion criteria and consent for recruitment will be randomly
divided into one of the two groups:

Group-1 [CLADS Group, n=15, Study group]: Anaesthesia will be induced and maintained with
propofol administered using the automated CLADS.

Group-2 [Manual Group, n=15, Control group]: Anaesthesia will be induced and maintained with
propofol administered using manually controlled infusion pumps titrated to BIS scores.

Sample-size Estimation In a previous multi-centre study, the percentage of time the BIS was
within 10 percentage of the target BIS was 81.4 percent in the CLADS group versus 55.34
percent in the manual group. Based on the above, to detect 20 percent difference in the two
groups, a sample size of 12 patients per group to provide 90 percent power with a bilateral
alpha risk value of 0.05 will be required. We plan to recruit a total of 30 patients to cover
up for unanticipated losses after the recruitment.

Randomisation, Allocation Concealment The patients will be randomly allocated to one of the
two groups based on a computer-generated random number table. Randomisation sequence
concealment will include opaque-sealed envelopes with alphabetic codes whose distribution
will be in control of an independent analyst. The envelopes will be opened; patient's
data-slip will be pasted on them, and will be sent back to the control analyst.

Blinding Strategy Inside the OR, the attending anaesthesiologist will not be blinded to the
technique utilised to administer GA and the recovery parameters immediately after extubation.
However, the postoperative patient recovery profile will be evaluated by an independent
assessor blinded to the GA technique and periextubation profile.

Management of Anesthesia Two peripheral venous lines (18G/20G catheter) will be secured.
Invasive vascular access (arterial line for direct continuous blood pressure assessment,
central venous catheter) will be secured as per the requirement of surgery. Standard
monitoring (EKG, NIBP, pulse oximeter, EtCO2) will be applied. A BIS sensor (Covidien IIc,
Mansfield, USA) will be applied over the patient's forehead according to manufacturer's
instructions (Model DSC-XP, Aspect medical system, USA) prior to induction of anaesthesia for
continuous monitoring of depth-of-anaesthesia.

Anaesthesia Technique

All the patients will receive pre-induction fentanyl-citrate 2 mcg/kg and anesthesia will be
induced with propofol. In the CLADS group, propofol administration rate will be controlled by
a feedback loop facilitated by BIS monitoring. A BIS value of 50 will be used as the target
point for induction and maintenance of anesthesia. The Manual group would comprise manual
propofol administration by an intravenous infusion pump to maintain a target BIS of 50 during
induction and maintenance of anesthesia.

After induction of anesthesia, atracurium besylate 0.05mg/kg will be given to facilitate
tracheal intubation. In order to facilitate one lung ventilation (OLV) patients trachea will
be intubated using appropriate-sized double-lumen tube in all the patients. Oxygen-air
mixture (FiO2 0.50) will be used for intraoperative ventilation in both the groups. In
addition, starting the period after tracheal intubation, all the patients will receive 1
mcg/kg/hr fentanyl infusion for intraoperative analgesia. Intraoperative muscle relaxation
will be maintained using atracurium infusion controlled by train-of-four response on
peripheral neuromuscular monitor (Infinity TridentNMT Smartpod, Draeger Medical Systems, Inc
Telford, USA).

In all patients undergoing open thoracic surgery, a thoracic epidural catheter will be placed
in the indicated intervertebral space for facilitating postoperative analgesia.

Thirty minutes before the end of surgery, non-opioid analgesics, such as paracetamol 1-gm,
tramadol 100 mg and/or diclofenac 75 mg will be administered to all the patients. Propofol
delivery will be stopped at the point of completion of skin closure. Residual neuromuscular
blockade (assessed with train-of-four response) will be reversed with neostigmine (50 µg/kg)
and glycopyrrolate (20 µg/kg). Tracheal extubation will be undertaken if planned
post-extubation ventilation is not instituted and the patients are wide awake and obeying
commands.

Assessment Parameters Intraoperative

1. Adequacy of anaesthesia depth will be determined by the percentage of the valid CLADS
time during which the BIS remained within 10% of the target BIS (50), median absolute
performance error (MDAPE), wobble and global score (Varvel criteria)

2. Haemodynamic parameters such a heart rate, non-invasive blood pressure will be recorded

3. Early recovery from anaesthesia profile which includes time to eye opening and time to
extubation after discontinuation of anesthesia will be noted

Postoperative

1. Sedation will be assessed using Modified Observer's assessment of alertness/sedation
scale.

2. Incidence of awareness will be determined using Modified Brice Questionnaire.

After discontinuation of anaesthesia delivery (0-time point) the time to eye opening and time
to extubation will be determined. After tracheal extubation, the patients will be shifted to
postoperative recovery room adjoining OT suites and will be closely observed for oxygenation
and ventilation status, pain (numeric rating score) and sedation. Patients with epidural
catheter in-situ will be started with PCEA pump for pain relief. Patients will be analysed
for intra-operative awareness using Modified Brice Questionnaire (24 hours, 48 hours
postoperatively).

Overall Status

Not yet recruiting

Start Date

2017-11-01

Completion Date

2018-12-01

Primary Completion Date

2018-11-01

Phase

Phase 4

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Anaesthesia depth consistency using BIS scores
From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively

Secondary Outcome

Measure

Time Frame

Evaluation of propofol anaesthesia delivery system
From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
Change in Intra-operative heart Rate (beats per minute)
From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
Change in Intra-operative systolic , diastolic, and mean (mmHg)
From beginning of anaesthesia (0-hours, baseline) till 10 hours intraoperatively
Recovery from anesthesia
From end of anaesthesia till 20-minutes postoperatively]
Recovery from anesthesia
From end of anaesthesia till 20-minutes postoperatively]
Intra-operative awareness
From the end of anaesthesia till 48-hours postoperatively

Enrollment

30

Conditions


Intervention

Intervention Type

Drug

Intervention Name


Description

Propofol delivery will be controlled using automated closed loop anaesthesia delivery system which will control propofol delivery rate to consistent anaesthetic depth (BIS-50) feedback from the patient (CLADS group)

Arm Group Label

CLADS group


Intervention Type

Drug

Intervention Name


Description

Propofol delivery will be controlled using infusion pumps which will be manually controlled to deliver propofol to maintain consistent anaesthetic depth (BIS-50). (Manual group)

Arm Group Label

Manual group



Eligibility

Criteria

Inclusion Criteria:

- ASA physical status I-III

- undergoing unilateral open thoracic surgery or unilateral video-assisted thoracic
surgery (VATS) Exclusion Criteria:

Exclusion Criteria:

- Uncompensated cardiovascular disease (e.g. uncontrolled hypertension,
atrio-ventricular block, sinus bradycardia, congenital heart disease, reduced LV
compliance, diastolic dysfunction)

- Hepato-renal insufficiency

- Uncontrolled endocrinology disease (e.g. diabetes mellitus, hypothyroidism)

- Known allergy/hypersensitivity to the study drug

- Drug dependence/substance abuse

- Requirement of postoperative ventilation

- Refusal to informed consent

Gender

All

Minimum Age

18 Years

Maximum Age

65 Years

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Goverdhan D Puri, MD, PhD
Study Chair
Post Graduate Institute of Medical Education & Research, Chandigarh, India
Jayashree Sood, MD,FFRCA
Study Director
Sir Ganga Ram Hospital

Overall Contact

Last Name

Nitin Sethi, DNB

Phone

00919717494498

Email



Location

Facility

Status

Contact

Investigator

Sir Ganga Ram Hospital
New Delhi Delhi 110060 India
Not yet recruiting
Last Name: Nitin Sethi, DNB
Phone: 00919717494498
Email: [email protected]
Last Name: Goverdhan D Puri, MD,PhD
Role: Sub-Investigator

Last Name: Bhuwan C Panday, MD
Role: Sub-Investigator

Last Name: Jayashree Sood, MD,FFRCA
Role: Sub-Investigator

Last Name: Shikha Sharma, MD
Role: Sub-Investigator

Last Name: Manish Gupta, MD
Role: Sub-Investigator

Last Name: Nitin Sethi, DNB
Role: Principal Investigator

Last Name: Amitabh Dutta, MD
Role: Principal Investigator


Location Countries

Country

India


Verification Date

2017-10-01

Lastchanged Date

2017-10-10

Firstreceived Date

2017-10-06

Responsible Party

Responsible Party Type

Sponsor-Investigator

Investigator Affiliation

Sir Ganga Ram Hospital

Investigator Full Name

Dr Nitin Sethi

Investigator Title

Associate Professor & Consultant


Keyword


Has Expanded Access

No

Condition Browse


Number Of Arms

2

Intervention Browse

Mesh Term

Anesthetics

Propofol



Arm Group

Arm Group Label

CLADS group

Arm Group Type

Active Comparator

Description

Anaesthesia will be induced and maintained with Propofol administered by CLADS. Its administration rate will be controlled by a feedback loop facilitated by BIS monitoring. A BIS value of 50 will be used as the target point for induction and maintenance of anaesthesia.


Arm Group Label

Manual group

Arm Group Type

Active Comparator

Description

Anaesthesia will be induced and maintained with propofol administration by an intravenous infusion pump. Its administration rate will be controlled manually to maintain a target BIS of 50 during induction and maintenance of anaesthesia.



Firstreceived Results Date

N/A

Overall Contact Backup

Last Name

Amitabh Dutta, MD

Phone

00919810848064

Email



Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Parallel Assignment

Intervention Model Description

30-patients aged 18-65 years, ASA physical status I-III, of either sex, and undergoing unilateral open thoracic surgery or unilateral video-assisted thoracic surgery (VATS) will randomly allocated by computer generated numbers to one of the following two groups of 15 patients each:
Group-1 [CLADS Group, n=15, Study group]: Anaesthesia will be induced and maintained with propofol administered using the automated CLADS.
Group-2 [Manual Group, n=15, Control group]: Anaesthesia will be induced and maintained with propofol administered using manually controlled infusion pumps titrated to BIS scores.

Primary Purpose

Basic Science

Masking

Double (Participant, Outcomes Assessor)

Masking Description

The patient will be blinded to the type of anaesthesia intervention.The attending anaesthesiologist will however not be blinded to the technique utilized to administer GA and recovery immediately after extubation inside the OR. The postoperative patient recovery profile will be evaluated by an independent assessor blinded to the technique of GA.


Study First Submitted

October 6, 2017

Study First Submitted Qc

October 10, 2017

Study First Posted

October 11, 2017

Last Update Submitted

October 10, 2017

Last Update Submitted Qc

October 10, 2017

Last Update Posted

October 12, 2017


ClinicalTrials.gov processed this data on October 12, 2017

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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